Prerandomization run-in periods in randomized controlled trials of chronic diseases: a methodological study.

OBJECTIVE: To systematically review the epidemiology of prerandomized run-in periods in randomized controlled trials (RCTs) of chronic diseases. STUDY DESIGN AND SETTING: Meta-epidemiologic study of all RCTs from the four highest impact medical journals from 2011 to 2016. Eligible trials included parallel RCTs that evaluated pharmacologic therapies in adults with chronic diseases with a minimum follow-up of 24 weeks. RESULTS: Of 262 eligible manuscripts, 48 (18.3%), representing 42 unique RCTs, included run-in periods. Run-in periods were most common in cardiovascular disease and diabetes trials. Of the 42 RCTs, in 22 patients received the experimental therapy, 15 placebo, 4 both (either sequentially or in combination), and one did not report the run-in period drug. The median run-in period duration was 28 days (Q1: Q3 14: 66 days). Reasons for including a run-in period included ensuring eligibility criteria were met (18, 42.9%), excluding participants with nonadherence (18, 42.9%) and intolerances to therapy (15, 35.7%), and to standardize therapy prior to randomization (8, 19.0%). The median run-in completion rate was 77.4% (Q1: Q3 62.2:87.8%). CONCLUSIONS: Run-in periods are uncommon in RCTs of chronic drug treatments and when used, their reporting is heterogeneous. Further research to improve the design, use, and reporting of run-in periods is necessary.

Transoral laser microsurgery and radiotherapy for oropharyngeal squamous cell carcinoma: Equitable survival and enhanced function compared with contemporary standards of care.

INTRODUCTION: We describe the 5-year oncological and functional outcomes of transoral laser microsurgery, neck dissection (TLM + ND) and adjuvant radiotherapy (PORT) used to treat patients with oropharyngeal carcinoma. The effectiveness of external carotid artery (ECA) ligation in reducing post-operative bleeding, and fibrin glue following ND in reducing wound drainage and length of hospital stay is reported. MATERIALS AND METHODS: This retrospective case review of consecutive patients undergoing TLM between 2006 and 2017 used the Kaplan-Meier Estimator and Log-Rank Test for univariate, time-to-event analyses, and Cox-Proportionate Hazard modelling for multivariate analysis. RESULTS: 264 consecutive patients were included. Mean follow-up was 49.4 months. 219 (82.9%) patients received PORT. Five-year overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) rates were 74.9%, 73.7%, and 86.2%, respectively. Five-year locoregional control was 89.4%. 65.5% of cases were Human papillomavirus associated (HPV+), for whom OS, DFS and DSS was 85.6%, 84.7% and 92.7%, respectively, and demonstrated significantly higher OS (hazard ratio (HR) 0.28, CI 0.16-0.49, p < 0.0001), DFS (HR 0.28, CI 0.17-0.47, p < 0.0001) and DSS (HR 0.2, CI 0.09-0.44, <0.001). Post-operative oropharyngeal bleeding occurred in 23 patients (8.7%), of which 5 were major/severe, in patients without ECA ligation. Fibrin glue significantly reduced neck drain output (p < 0.001), and length of hospital stay (p < 0.001). One-year gastrostomy dependence rate was 2.3%. CONCLUSIONS: TLM + ND + PORT results in favourable 5-year survival and locoregional control rates, and low feeding tube dependency rates. ECA ligation and fibrin glue appear to reduce major post-operative haemorrhage, wound drainage and length of hospital stay.

Screening questions for the diagnosis of restless legs syndrome in hemodialysis.

BACKGROUND: Restless legs syndrome (RLS) is common in end-stage renal disease and is associated with reduced health-related quality of life. Simple and accurate screening instruments are needed since RLS is underdiagnosed and treatable. We examined the operating characteristics of screening questions and a disease-specific measurement tool for the diagnosis of RLS in hemodialysis. METHODS: We conducted a cohort study of prevalent adult hemodialysis patients in Hamilton, Canada. The diagnosis of RLS was made using the 2012 Revised International Restless Legs Syndrome Study Group (IRLSSG) criteria. All participants received three screening instruments: (i) a single screening question for RLS derived from a nondialysis population; (ii) a single question from the Edmonton Symptom Assessment System (ESAS); and (iii) the IRLSSG Rating Scale (IRLS). All instruments were compared with the reference standard using logistic regression from which receiver operating characteristics curves were generated. Cutoffs associated with maximum performance were identified. RESULTS: We recruited 50 participants with a mean (SD) age of 64 (12.4) years, of whom 52% were male and 92% were on three times weekly hemodialysis. Using the reference standard, 14 (28%) had a diagnosis of RLS. The single screening question for RLS had an area under the receiver operating curve (AUROC) of 0.72 with a sensitivity of 85.7% and specificity of 58.3%. An ESAS cutoff of ≥1 had the highest AUROC at 0.65 with a sensitivity of 79% and specificity of 56%. An IRLS cutoff of ≥20 had the highest AUROC at 0.75 with a sensitivity of 71% and specificity of 81%. CONCLUSION: IRLS had better specificity than the single question or ESAS for the diagnosis of RLS.

High dose of dexamethasone protects against EAE-induced motor deficits but impairs learning/memory in C57BL/6 mice.

Multiple sclerosis (MS) is an autoimmune and neuroinflammatory disease characterized by demyelination of the Central Nervous System. Immune cells activation and release of pro-inflammatory cytokines play a crucial role in the disease modulation, decisively contributing to the neurodegeneration observed in MS and the experimental autoimmune encephalomyelitis (EAE), the widely used MS animal model. Synthetic glucocorticoids, commonly used to treat the MS attacks, have controversial effects on neuroinflammation and cognition. We sought to verify the influence of dexamethasone (DEX) on the EAE progression and on EAE-induced cognitive deficits. In myelin oligodendrocyte glycoprotein peptide (MOG35-55)-induced EAE female mice, treated once with DEX (50 mg/kg) or not, on the day of immunization, DEX decreased EAE-induced motor clinical scores, infiltrating cells in the spinal cord and delayed serum corticosterone peak. At the asymptomatic phase (8-day post-immunization), DEX did not protected from the EAE-induced memory consolidation deficits, which were accompanied by increased glucocorticoid receptor (GR) activity and decreased EGR-1 expression in the hippocampus. Blunting hippocampal GR genomic activation with DnGR vectors prevented DEX effects on EAE-induced memory impairment. These data suggest that, although DEX improves clinical signs, it decreases cognitive and memory capacity by diminishing neuronal activity and potentiating some aspects of neuroinflammation in EAE.

Single Questions for the Screening of Anxiety and Depression in Hemodialysis.

BACKGROUND: Depression and anxiety are common and underrecognized in end-stage renal disease (ESRD), are associated with poor outcomes and reduced health-related quality of life, and are potentially treatable. Simple, accurate screening tools are needed. OBJECTIVE: We examined the operating characteristics of single questions for anxiety and depression from the Edmonton Symptom Assessment System (ESAS) in hemodialysis. DESIGN: Cross-sectional study. SETTING: Two outpatient hemodialysis units (1 tertiary, 1 community) in Hamilton, Canada. PATIENTS: Adult prevalent hemodialysis patients. MEASUREMENTS: ESAS and Hospital Anxiety and Depression Scale (HADS). METHODS: Participants were asked the degree to which they experienced anxiety and depression using the ESAS. ESAS single questions for anxiety and depression were compared with the reference standard of the HADS using dialysis population specific cutoffs (HADS anxiety subscale ≥6 and HADS depression subscale ≥7). Logistic regression was used to create receiver operating characteristics (ROC) curves. RESULTS: We recruited 50 participants with a mean age of 64 (SD = 12.4) years, of whom 52% were male and 96% were on ≥3× weekly hemodialysis. Using the reference standards, 28 (56%) had a diagnosis of anxiety and 27 (54%) had a diagnosis of depression. Areas under the ROC curves were 0.83 for anxiety and 0.81 for depression using ESAS scores of ≥2. LIMITATIONS: Sample size and the lack of a reference gold standard. CONCLUSIONS: The ESAS single questions for anxiety and depression have reasonable discrimination in a hemodialysis population. The use of more complex and time-consuming screening instruments could be reduced by adopting the ESAS questions for anxiety and depression in hemodialysis.

CONTEXTE: La dépression et l'anxiété sont fréquentes quoique peu reconnues chez les patients souffrant d'insuffisance rénale terminale (IRT). Ces troubles sont associés à une évolution défavorable de la maladie et à une diminution de la qualité de vie liée à l'état de santé. Cependant, ils sont potentiellement traitables. Des outils de détection simples et précis sont requis. OBJECTIF: Nous avons évalué la fonction d'efficacité de questions uniques sur l'anxiété et la dépression provenant du Système d'évaluation des symptômes d'Edmonton (ESAS) en contexte d'hémodialyse. TYPE D'ÉTUDE: Étude transversale. CADRE: Deux unités d'hémodialyse ambulatoire (une en soins tertiaires, une en milieu communautaire) à Hamilton, au Canada. SUJETS: Des patients adultes hémodialysés. MESURES: L'ESAS et l'Échelle d'anxiété et de dépression en milieu hospitalier (HADS). MÉTHODOLOGIE: Nous avons demandé aux participants, par l'entremise de l'ESAS, dans quelle mesure ils éprouvaient de l'anxiété et de la dépression. Les questions uniques de l'ESAS sur l'anxiété et la dépression ont été comparées à l'étalon de référence de la HADS en utilisant les seuils spécifiques à une population dialysée (sous-échelle de la HADS pour l'anxiété ≥ 6 et sous-échelle de la HADS pour la dépression ≥ 7). Une régression logistique a été utilisée pour établir les courbes de fonction d'efficacité de l'observateur (courbes ROC). RÉSULTATS: Nous avons recruté 50 patients (52 % d'hommes) âgés de 64 ans en moyenne (écart-type : 12,4 ans). La plupart des sujets (96 %) étaient dialysés au moins trois fois par semaine. Selon l'étalon de référence, 28 patients (56 %) vivaient de l'anxiété et 27 (54 %) souffraient de dépression. La surface sous la courbe ROC était de 0,83 pour l'anxiété et de 0,81 pour la dépression selon les scores ESAS ≥ 2. LIMITES: Le faible échantillon de sujets et le fait que l'étude ne comportait pas d'étalon-or. CONCLUSION: Les questions uniques de l'ESAS sur l'anxiété et la dépression ont discriminé adéquatement dans une population de patients hémodialysés. L'adoption du questionnaire ESAS sur l'anxiété et la dépression avec les patients hémodialysés pourrait limiter le recours à des outils de détection chronophages et complexes.

Infestation by Chiggers ( Hannemania sp.) of Miranda's White-lipped Frog ( Leptodactylus macrosternum) from a Semiarid, Neotropic Region of Brazil.

We identified Miranda's white-lipped frog ( Leptodactylus macrosternum) as a new host for chiggers ( Hannemania sp.). A total of 57 larvae of Hannemania sp. were found on 31 frogs examined from a semiarid region of northeastern Brazil.

IgA Nephropathy.

IgA nephropathy (IgAN) is a leading cause of CKD and renal failure. Recent international collaborative efforts have led to important discoveries that have improved our understanding of some of the key steps involved in the immunopathogenesis of IgAN. Furthermore, establishment of multicenter networks has contributed to rigorous design and execution of clinical trials that have provided important insights regarding immunotherapy in IgAN. In this article, we review emerging developments in clinical and translational IgAN research and describe how these novel findings will influence future strategies to improve the outcome of patients with IgAN.

Transoral laser microsurgery for oropharyngeal squamous cell carcinoma: A paradigm shift in therapeutic approach.

BACKGROUND: The contemporary treatment of oropharyngeal squamous cell carcinoma (SCC) is an area of debate. We report outcomes of a minimally invasive approach involving transoral laser microsurgery (TLM). METHODS: A consecutive series of patients (n = 153) undergoing primary TLM for oropharyngeal SCC from 2006 to 2013 was studied. Human papillomavirus (HPV) status was determined by p16 immunohistochemistry and high-risk HPV DNA in situ hybridization. Survival analyses were evaluated using Kaplan-Meier statistics. RESULTS: Tumor subsites included tonsil (n = 94; 61.5%), tongue base (n = 38; 24.8%), and soft palate (n = 21; 13.7%), with the majority being American Joint Committee on Cancer (AJCC) stage III/IVa (n = 124; 81.0%) and HPV-positive (n = 101; 66.0%). Three-year overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were 84.5%, 91.7%, and 78.2%, respectively. HPV-positivity portended favorable oncologic outcomes. One-year gastrostomy tube (G-tube) dependency was 1.3%. CONCLUSION: To the best of our knowledge, this is the largest single-center TLM oropharyngeal SCC series to date. Our data suggest that TLM +/- postoperative radiotherapy (PORT) results in at least as good oncologic outcomes as chemoradiotherapy (CRT), while conferring swallowing function advantages. © 2016 Wiley Periodicals, Inc. Head Neck , 2016 © 2016 Wiley Periodicals, Inc. Head Neck 38:1263-1270, 2016.

Conhecimento de auxiliares de higienização sobre limpeza e desinfecção relacionados à infecção hospitalar / Conocimiento de auxiliares de higienización sobre limpieza y desinfección relacionados a la infección hospitalaria / Knowledge of housekeeping cleaners about cleaning and disinfection related to hospital infection

Objetivo: identificar o conhecimento dos auxiliares de higienização sobre limpeza e desinfecção, relacionados à prevenção de Infecção Hospitalar. Método: pesquisa qualitativa, descritiva, realizada com 31 auxiliares de higienização de um hospital geral no sul de Minas Gerais. A coleta ocorreu entre setembro e outubro de 2013, por meio de entrevistas abertas. Os dados foram analisados segundo o referencial teórico de Minayo, pela análise de conteúdo e agrupados nas categorias: conhecimento sobre infecção hospitalar e realização dos procedimentos de limpeza e desinfecção. Resultados: as participantes demonstraram pouco conhecimento sobre infecção hospitalar e descreverama realização dos procedimentos de limpeza e desinfecção, porém apresentaram falhas na realização destes procedimentos. Identificaram a importância de seu trabalho embora mencionassem insatisfação pela falta de reconhecimento e valorização profissional.Conclusão: os resultados evidenciaram a necessidade de capacitação no dia a dia de trabalho destes profissionais.

Aim: to identify the knowledge of housekeeping cleaners of cleaning and disinfection, related to prevention of hospital infection. Method: qualitative, descriptive research, carried out with 31 housekeeping cleaners of a general hospital in the south of Minas Gerais. The data collection occurred between September and October 2012, through open interviews. Data were analyzed according to the theoretical framework of Minayo, through content analysis, and were grouped into the categories: knowledge of hospital infection and performing disinfection and cleaning procedures. Results: participants showed little knowledge of hospital infection and described the cleaning and disinfectionprocedures, but there were flaws in performing these procedures. They identified the importance of their work, despite mentioning dissatisfaction by the lack of recognition and professional development. Conclusion: the results showed the need for training in day to day work of these professionals.

Objetivo: identificar el conocimiento de los auxiliares de higienización sobre procedimientos de limpieza y desinfección, relacionados a la prevención de Infección Hospitalaria. Método: investigación qualitativa, descriptiva, realizada con 31 auxiliares de higienización de un hospital general, del Sur de Minas Gerais. La coleta ocurrió entreseptiembre y octubre de 2013, a través de entrevistas abiertas. Se analizaron los datos según el marco teórico de Minayo, por el análisis del contenido y agrupados en las categorías: conocimiento sobre la infección hospitalaria y la realización de los procedimientos de limpieza y desinfección. Resultados: las participantes demostraronpoco conocimiento sobre infección hospitalaria y describieron los procedimientos de limpieza y desinfección, todavía presentaron errores en la realización de estos. Identificaron la importancia de su trabajo aunque mencionasen la insatisfacción por la falta de reconocimiento y valoración profesional. Conclusión: los resultados evidenciaronla necesidad de capacitación del trabajo de estos profesionales.

A tumour lysis syndrome in a chemotherapy naïve patient with metastatic pancreatic adenocarcinoma.

A 56-year-old woman with a new diagnosis of metastatic pancreatic cancer presents to the emergency room with generalised fatigue. The patient is afebrile, however, hypotensive and tachycardic. Physical examination shows diffuse lymphadenopathy. Initial laboratory tests indicate that the patient has hyperkalaemia, hypocalcaemia, with a high lactate dehydrogenase and high uric acid. The patient was also in renal failure. On the basis of the clinical presentation, the patient was diagnosed with spontaneous tumour lysis syndrome, despite the syndrome never having been reported in metastatic pancreatic cancer. The patient was treated appropriately with intravenous hydration, allopurinol and rasburicase. All laboratory abnormalities were corrected by day 3 of treatment.

Evaluación de la variabilidad de la dimensión vertical de oclusión en niños y adolescentes / Evaluation of variability of vertical dimension of occlusion in children and adolescents

La reproducción correcta de la dimensión vertical de oclusión es la base para la mantención de la salud del sistema estomatognático.Algunos métodos permiten la medición facial de forma reproducible, como la comparación de la distancia Comisura labial – Ángulo del ojo, así como la distancia Nasion-Menton. El objetivo de este trabajo fue evaluar la medida de la Dimensión Vertical de Oclusión y sucorrelación con género en niños y adolescentes. Fueron evaluados 176 individuos, de los cuales 48 fueron selecionados dentro de los criterios de inclusión. La medida de la dimensión vertical de oclusión fue realizada por medio de calibrador digital y fue registrada en fichas individuales. Los datos fueron estratificados por grupo etáreo y analizados por el T-test. Valores de p menores a 0,05 fueronconsiderados significantes. Los resultados evidenciaron que la Dimensión Vertical de Oclusión demostró medidas distintas por grupoetáreo y género, variando de 47,70 mm a 70,20 mm para Ángulo externo del ojo-Comisura labial y 52, 30 mm a 70,60 mm para Nasion – Menton, en el género femenino. Se observó alteración estadísticamente significativa entre estas distancias en las edades de 10 y 12 años en el género masculino, mientras que para el género femenino no fue constatada diferencia significativa, considerando el nivel designificancia de 5%. Se concluye que es necesario el registro correcto de la Dimensión Vertical de Oclusión para la reproducción de esta medida, respetándose la diferenciación por grupo etáreo y género, dado que las alteraciones de la Dimensión Vertical de Oclusión pueden llevar al paciente a alteraciones oclusales, musculares y articulares, además de predisposición a maloclusiones.

The correct reproduction of the vertical dimension of occlusion (VDO) is the basis for restoring health to the stomatognathic system. A number of methods allow facial measurement in a safe, reproducible manner, such as the comparison of distance from the lipcommissure to corner of the eye (LC-CE) to the distance from the base of the nose to the chin (N-Ch). The aim of the present study was to determine VDO length in children between 7 and 12 years of age and the correlation of this length with gender. One hundredseventy-six children were evaluated, among which 48 fulfilled the inclusion criteria. The data were stratified by age and analyzed using the paired Student’s t-test. All p-values less than 0.05 were considered statistically significant. There were different measures of VDOwith regard to age and gender, ranging from 52.30 mm to 70.20 mm for the LC-CE distance and 52.30 mm to 70.60 mm for the N-Ch distance in the girls. There was no statistically significant difference between these distances in the ages of 10 and 12 years for malesand that the correlation between LC-EC and N-Ch was not significant for females. For women, there was a correlation between LC-EC and N-Ch, considering the significance level of 5%. There was conclude that it is necessary to measure the correct VDO and standard measures for reproduction of this measure, while the differentiation by age and gender, since the change in VDO can lead the patientto occlusal changes, muscle and joint pain, beyond the predisposition to malocclusion.

Normal human monocytes exposed to glioma cells acquire myeloid-derived suppressor cell-like properties.

Glioblastoma patients are immunosuppressed, yet glioblastomas are highly infiltrated by monocytes/macrophages. Myeloid-derived suppressor cells (MDSC; immunosuppressive myeloid cells including monocytes) have been identified in other cancers and correlate with tumor burden. We hypothesized that glioblastoma exposure causes normal monocytes to assume an MDSC-like phenotype and that MDSC are increased in glioblastoma patients. Healthy donor human CD14(+) monocytes were cultured with human glioblastoma cell lines. Controls were cultured alone or with normal human astrocytes. After 48 hours, glioblastoma-conditioned monocytes (GCM) were purified using magnetic beads. GCM cytokine and costimulatory molecular expression, phagocytic ability, and ability to induce apoptosis in activated lymphocytes were assessed. The frequency of MDSC was assessed by flow cytometry in glioma patients' blood and in GCM in vitro. As predicted, GCM have immunosuppressive, MDSC-like features, including reduced CD14 (but not CD11b) expression, increased immunosuppressive interleukin-10, transforming growth factor-beta, and B7-H1 expression, decreased phagocytic ability, and increased ability to induce apoptosis in activated lymphocytes. Direct contact between monocytes and glioblastoma cells is necessary for complete induction of these effects. In keeping with our hypothesis, glioblastoma patients have increased circulating MDSC compared with normal donors and MDSC are increased in glioma-conditioned monocytes in vitro. To our knowledge, this has not been reported previously. Although further study is needed to directly characterize their origin and function in glioblastoma patients, these results suggest that MDSC may be an important contributor to systemic immunosuppression and can be modeled in vitro by GCM.